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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
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β-lactam antibiotic concentrations during continuous renal replacement therapy.
Critical Care (London, England)
|June 3, 2014
Summary
Standard beta-lactam antibiotic doses in continuous renal replacement therapy (CRRT) often achieve adequate levels. However, many patients experience very high drug concentrations, suggesting dose adjustments may be necessary for septic patients on CRRT.
Area of Science:
- Pharmacology
- Nephrology
- Intensive Care Medicine
Background:
- Standard beta-lactam antibiotic doses may be insufficient in patients undergoing continuous renal replacement therapy (CRRT).
- Evaluating the adequacy of unadjusted antibiotic regimens in CRRT patients is crucial for effective treatment.
Purpose of the Study:
- To assess the efficacy of standard beta-lactam antibiotic doses in patients receiving CRRT.
- To determine the impact of CRRT intensity on antibiotic drug clearance and serum concentrations.
Main Methods:
- A retrospective review of 50 adult intensive care patients receiving CRRT was conducted.
- Therapeutic drug monitoring (TDM) of ceftazidime/cefepime, piperacillin/tazobactam, and meropenem was performed using high-performance liquid chromatography (HPLC-UV).
- Adequacy was defined by serum drug concentrations relative to Pseudomonas aeruginosa minimum inhibitory concentration (MIC) thresholds.
Main Results:
- 90% of samples showed drug concentrations above 4 times the MIC, indicating generally adequate levels.
- However, 53% of samples had concentrations exceeding 8 times the MIC, suggesting potential for supra-therapeutic levels.
- Drug concentrations were similar in early (ET) and late (LT) phases of CRRT, with a weak correlation between clearance and CRRT intensity.
Conclusions:
- Unadjusted beta-lactam antibiotic doses achieved adequate therapeutic drug levels in most septic patients on CRRT.
- A significant proportion of patients experienced very high drug concentrations, necessitating consideration of dose adjustments.
- The findings highlight the need for individualized dosing strategies in CRRT patients to optimize antibiotic therapy and minimize toxicity.
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